THE CARDIOTOXIC EFFECTS OF BUPIVACAINE DE PEND ON THE STIMULATION FREQUENCY OF A CARDIAC-PACEMAKER - RESULTS OF AN EXPERIMENTAL-STUDY IN PIGS

The cardiotoxic effects of bupivacaine are related to the temporal dis persion of effective refractory periods in different parts of the card iac conduction system. This effect facilitates the occurrence of re-en try arrhythmias under burst stimulation [4, 8]. In this study physiolo gical increments in heart rate were simulated by cardiac pacing, and t he electrophysiological and haemodynamic effects under the influence o f cardiotoxic concentrations of bupivacaine were measured. Methods. Af ter institutional approval we generated cardiotoxic arterial plasma co ncentrations of bupivacaine (6.9 +/- 1.6 mul/ml) in pigs (n = 8; 15-22 kg) by i.v. injection of 4 mg bupivacaine/kg, followed by a constant rate infusion of 0.2 mg/kg per min [8]. The pigs were anaesthetized wi th midazolam, fentanyl and pancuronium and normoventilated with a FiO2 of 0.4. Internal right atrial and right ventricular pacing was perfor med with increasing frequencies of 20, 40, 60, 80 and 100 stimulations /min above individual spontaneous heart rates (AL) before (control) an d after the administration of bupivacaine. ECG, MAP, LVSP, dp/dt(max) and stimulation thresholds were recorded. Student' s t-test, and the U -test of Wilcoxon, Mann and Whitney were used for statistical testing with a significance level of 0.05. Results. By inducing a frequency-de pendent increase in stimulation threshold, bupivacaine prevented regul ar atrial pacing with frequencies higher than AL+60. Ventricular pacin g with a frequency of AL+40 induced a lethal arrhythmia in 1 animal. I n the remaining 7 pigs ventricular pacing showed a frequency-dependent increase in stimulation thresholds (Fig. 1) and stimulus-QRS interval s (Fig. 5), MAP (Fig. 2), LVSP (Fig. 3) and cardiac inotropy (Fig. 4) showed frequency-dependent decreases under ventricular pacing. Conclus ions. The toxic effects of bupivacaine on pacing thresholds, av conduc tion, intraventricular conduction, cardiac inotropy, and blood pressur e are modulated by the stimulation frequency of a cardiac pacemaker. T he cardiotoxic effects of bupivacaine seem to be use dependent. Even m inor increments in heart rate can induce malignant arrhythmias. Cardia c pacing can be difficult in the presence of toxic bupivacaine concent rations, and high-frequency pacing should be avoided. It has to be ver ified whether higher heart rates generated by the physiological pacema kers of the heart do also increase the cardio-circulatory toxicity of bupivacaine. If that holds true, drugs that can induce tachycardias sh ould be avoided in the treatment of bupivacaine toxicity.